title: Calculation of Tajima's D and other neutrality test statistics from low depth next-generation sequencing data.
abstract: BACKGROUND
  A number of different statistics are used for detecting natural selection using DNA sequencing data, including statistics that are summaries of the frequency spectrum, such as Tajima's D. These statistics are now often being applied in the analysis of Next Generation Sequencing (NGS) data. However, estimates of frequency spectra from NGS data are strongly affected by low sequencing coverage; the inherent technology dependent variation in sequencing depth causes systematic differences in the value of the statistic among genomic regions.
  
  
  RESULTS
  We have developed an approach that accommodates the uncertainty of the data when calculating site frequency based neutrality test statistics. A salient feature of this approach is that it implicitly solves the problems of varying sequencing depth, missing data and avoids the need to infer variable sites for the analysis and thereby avoids ascertainment problems introduced by a SNP discovery process.
  
  
  CONCLUSIONS
  Using an empirical Bayes approach for fast computations, we show that this method produces results for low-coverage NGS data comparable to those achieved when the genotypes are known without uncertainty. We also validate the method in an analysis of data from the 1000 genomes project. The method is implemented in a fast framework which enables researchers to perform these neutrality tests on a genome-wide scale.
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oestervoldgade 5-7, DK-1350, Copenhagen, Denmark. thorfinn@binf.ku.dk.
authors.forename: Thorfinn Sand
authors.initials: TS
authors.lastname: Korneliussen
authors.forename: Ida
authors.initials: I
authors.lastname: Moltke
authors.forename: Anders
authors.initials: A
authors.lastname: Albrechtsen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
mesh_terms: D001483:Base Sequence; D001499:Bayes Theorem; D015982:Bias; D005240:Feasibility Studies; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation; D005828:Genetics, Population / Q000706:statistics & numerical data*; D015894:Genome, Human; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000706:statistics & numerical data; D006801:Humans; D016013:Likelihood Functions; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*